Narcqtine camphosulfonate



United States Patent 3,108,106 NARCOTINE CAMPHOSULFONATE Jacques Maillard, Paris, France, assignor to Societe dilxploitation des Laboratoires Jacques Logeais, Issy-les- Moulineaux, France No Drawing. Filed July 29, 1960, Ser. No. 46,088 Claims priority, application Belgium July 30, 1959 1 Claim. ((11. 260-285) It is the object of the present invention to provide, by way of novel industrial product, a new salt of (l) narcotine, that is, (dl-) camphosulfonate, corresponding to the formula:

=0 & -CH3 I OCH:

This invention is also concerned with a method of preparing a well-defined narcotine salt of which the solubility in water is such as to permit its use in therapeutics in the form of injectable solution as well as in pharmaceutic form for oral administration.

Narcotine camphosulfonate is advantageous in that it combines the analeptic respiratory and cardiovascular properties of camphousulfonic acid with the spasmolytic and bronchodilating action of narcotine.

MODE or PREPARATION 8.26 grams (.02 M) of (l-) narcotine base are added by small fractions to a solution consisting of 4.64 grams (.02 M) of pure (dl-) camphosulfonic acid in 100 cc. of 96-degree ethanol. The dissolution is completed by heating a few minutes at 40 to 50 C.

The filtered solution is then evaporated to dryness in vacuo; the amorphous residue (13 grams) is redissolved in the cold in 100 cc. of ethyl acetate. The crystals are left overnight at 0 C. and subsequently washed firstly with ethyl acetate and then with purified ether, and finally dried in vacuo.

Weight: 11 grams; yield: 85%.

PROPERTIES White needles completely soluble in water at soluble in methanol and ethanol. scarcely soluble in ethyl acetate but insoluble in purified ether.

M.P. (capillary tube)=1*88 to 191 C.

At 33 C., a (rotatory power)=+32 7 (at a concentration c.=4.56% in water).

Loss of weight at 110=.16%.

Percent of camphosulfonic acid: 36.65

(theoret,=35.97%) (acidimetric proportion) C=59.38-59.37 (theoret.=59.51%). H=6.01-5.96 (theoret.=6.05%).

The narcotine camphosulfonate according to this invention was administered in the form of compressed tablets 3,198,165 Patented Oct. 22, 1963 to patients suffering from various forms of acute or chronic pneumopathy with more or less pronounced coughing, this symptom being attended by mucous or muco-purulent expectoration.

All the patients were males and aged from 25 to 67. Various types of pneumopathies observed:

(1) Acute Diseases (2) Chronic Diseases 6 chronic bronchites, some of which being secondary to a stabilized tuberculosis.

2 evolutive pleuro-pulmonar tuberculoses.

5 cancers of the lungs.

2 silicoses (pneumonokonioses).

l asthma.

It is worth noting the usual difliculty of treating functional troubles in these chronic patients who have been coughing for years.

TOLERANCE The product is always well tolerated and does not produce digestive, cutaneous, neurological or blood troubles.

In three cases the patients noted themselves, from the very second day of the treatment, a considerable increase in the expectoration (50 to cc. daily).

RESULTS The product was administered in quantities ranging from 50 to 200 milligrams, that is, 1 to 4 tablets daily taken by fractions; actually, it can be administered in the form of compressed tablets containing 50 mg. of the product, with the usual excipients, or in the form of suppositories containing 50 mg. of the product, or in the form of sirup containing 100 mg. of the product in 250 cc. of flavored sugar sirup.

The improvement was observed the most in all the favorable cases.

In 17 patients the cough was soothed; these were the five cases of acuate pneumopathies indicated hereinabove, and twelve cases of chronic bronchopathies.

The average dose adopted was 100 to mg. daily, and one patient was a definite success with only 50 mg.

The four failures were all chronic patients of which the diseases had developed during several years; they were one bronchitic, one intricated asthma, one silicosis diagnosed 18 months before with a considerable nodular and emphysematous lesion and a lung cancer with abscessed atelectasis.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

The method of preparing narcotine camphosulfonate which comprises the steps of adding (l) narcotine base by small fractions to a solution of pure camphosulfonic acid in ethanol, completing the dissolution by heating to 40 to 50 C., filtering and evaporating to dryness in vacuo, dissolving the amorphous residue in ethyl acetate, allowing the camphosulfonate crystals to develop, washing these crystals and drying same in vacuo.

within 48 hours at (References on foliowing page) References Cited in the file of this patent (1911), citing Perkin et a1., Pros. Chem. 500., volume 26,

UNITED STATES PATENTS page; 131'. 1 Ab t t 1 37 6407 (1943) nemica s rac s, vo ume page 215451094 al 1951 citing Mercier et 211., J. Pharm. Chem. 9 1, 287-92 OTHER REFERENCES 5 1940 Chemical Abstracts (I), Decennial Index, volumes 1- Karrer Organic Chemistry 2nd edition, Pages 92402 10, pages 372526 (1907-1916), Subject Index.

Chcmical Abstracts II, volume 5, pages 864-865 MifZa 6181-, Nature, Volume 166, P g 271-2 

